prevention of secondary infections by interferon gamma in icu-acquired sustained immune-suppression

Conditions: Sustained Immunosuppression

Summary: the goal of this clinical trial is to demonstrate the benefit of a standardized immunotherapy (interferon gamma) on the incidence of secondary infections. . it will also learn about the safety of interferon-gamma. the main questions it aims to answer are: does interferon-gamma: * reduces the incidence of secondary infection episodes at three months * reduces the icu mortality and at day 90 * reduces the icu and hospital length of stay * induces biological immune restoration at day 10 * has cost-consequence and cost-effectiveness researchers will compare interferon-gamma to a placebo (a look-alike substance that contains no drug) to see if interferon-gamma works to treat sustained immunosuppression . participants will: * take interferon-gamma or a placebo for a maximum of 5 times between day 1 and day 9 * be monitored evety day until their icu discharge and at day 30, 60 and 90


Eligibility criteria:
inclusion criteria: * adult patient hospitalized in the icu for at least 1 week * expected length of stay in the icu greater than 10 days at screening * at least 1 episode of multiple organ failure, defined as a sofa ≥ 6 (excluding the respiratory component when related to a neurological failure), during the first 1 week of icu hospitalization * immunosuppression defined as an mhla-dr \< 8000 ab/c and a lymphopenia \< 1000/mm3 within a 96 hours time window * patient or the legal representative giving consent must be able to understand the trial in its entirety * patient affiliated to the social security system * for female participants of childbearing potential, agreement to use dual methods of contraception until day 90 * for male participants with female partners of childbearing potential, agreement to use barrier method of contraception until day 90. exclusion criteria: * uncontrolled secondary infections ongoing at the time of screening * participation in another research clinical trial within 30 days * chemotherapy / radiation therapy within the last 6 weeks * apache ii ≥ 30 at screening * history of autoimmune disease * organ or bone marrow transplant * history of hematologic malignancy * history of hepatitis c * hiv stage c within the last 12 months * patients under legal protection * history of or ongoing tuberculosis * chronic hepatitis b * patients receiving immunosuppressive medications including patient receiving a steroid dose greater than 1mg/kg/day of prednisone equivalent for more than 1 week and patient that have been on corticosteroid for more than 3 months * patient with thrombocytopenia below 50,000/mm3 * patient with traumatic brain and spinal injury * pregnancy or breast feeding * subjects with a history hypersensitivity to interferon gamma or excipient (mannitol, sodium succinate dibasic hexahydrate, succinic acid, polysorbate 20), known latex hypersensitivity or other interferon * hepatic cytolysis with ast/alt \> 5 times uln (local laboratory) * suspected acute pancreatitis with lipase or amylase \> 3 times uln (local laboratory) * severe chronic renal failure (egfr\<10 ml/min/1.73m2 ckp-epi method) * acute ecg abnormality such as myocardial infarction or any acute life-threatening ecg abnormalities (e.g: ventricular fibrillation, ventricular tachycardia...) * mental state rendering the person giving consent incapable of understanding the trial * patient deprived of liberty by judicial or administrative decision * patient being the investigator, or any member of the team or relative of the investigator directly involved in the trial, including assistant doctors, pharmacists, nurses, trial coordinators

Keywords: icu immuno-restauration secondary infections prevention